Is EDIL3 p.Phe437Cys (c.1310T>G) pathogenic?

EDIL3 p.Phe437Cys (c.1310T>G) is classified Uncertain significance in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.8668); Rare (popmax 0.107%, eas).

How common is EDIL3 p.Phe437Cys (c.1310T>G) in the general population?

EDIL3 p.Phe437Cys (c.1310T>G) is rare (popmax 0.107%, eas) (gnomAD).

What do computational predictors say about EDIL3 p.Phe437Cys (c.1310T>G)?

AlphaMissense predicts likely pathogenic (score 0.8668) — an in-silico prediction, not a clinical call.

EDIL3 p.Phe437Cys

c.1310T>G · VCV4246619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8668 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8668	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 20 kb · p 0.00012 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% East Asian · 48/44,654 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0747%

Overall 0.00304% 49/1,612,200 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.107%	930
Remaining individualsnot grpmax-eligible	0.0016%	62,390

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EDIL3
Protein: p.Phe437Cys
Coding: c.1310T>G
MANE Select: NM_005711
Type: single nucleotide variant
Location: chr5:83943552 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 437: a disulfide bond; the f5/8 type c 2 domain

Full EDIL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDIL3 p.Ala396Thr Uncertain significance ★ ⚠ same type
EDIL3 p.Ala42Val Uncertain significance ★ ⚠ same type
EDIL3 p.Ala75Ser Uncertain significance ★ ⚠ same type
EDIL3 p.Ala75Thr Uncertain significance ★ ⚠ same type
EDIL3 p.Arg181Gln Uncertain significance ★ ⚠ same type
EDIL3 p.Arg212Ser Uncertain significance ★ ⚠ same type
EDIL3 p.Arg272Cys Uncertain significance ★ ⚠ same type
EDIL3 p.Arg272His Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/edil3-p-phe437cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown